Upper respiratory tract infections (URIs) include a group of illnesses that can be mild to life-threatening where the upper respiratory tract is the main affected part. The infecting organism can affect the sinuses, the nasal passages, the pharynx or the larynx. Several diseases can be put under the umbrella of URIs which include rhinitis, pharyngitis, sinusitis, epiglottitis, laryngitis and tracheitis.

Definition of Upper Respiratory Tract Infection

Rhinitis can be defined as the inflammation of the nasal mucosa, which is found in some allergic conditions. Patients with sinusitis have inflammation of the paranasal sinuses which include the frontal, ethmoid, maxillary and sphenoid sinuses.

Rhinopharyngitis is the inflammation of the nasal passages, the pharynx, and the tonsils. The common cold usually results in rhinopharyngitis. Patients with epiglottitis can have bacterial etiology and the condition might be life-threatening.

Epidemiology of URIs

URIs are considered as the most common infectious diseases in the population. Patients can develop the common cold up to four times per year for adults, and eight times per year for children. Viral and bacterial pharyngitis are common in children and account for 1% of the outpatient clinic visits.

Image: “Acute epiglottitis; lateral view in X-ray imaging. The lateral soft-tissue radiograph reveals the “thumb sign” that indicates a swollen epiglottis, suggestive of epiglottitis. The diagnosis was confirmed on subsequent imaging and laryngoscopy. The patient recovered following treatment with predonine and ceftriaxone.” by Med Chaos – Own work. License: CC0 1.0

Sinusitis in patients with uncomplicated URIs is common and can be identified in up to 80% of the cases. Fortunately, bacterial sinusitis is only found in 2% of the cases.

Epiglottitis is usually caused by Haemophilus influenzaeinfection and since the introduction of Hib vaccine, the incidence of epiglottitis decreased significantly. The current incidence of acute epiglottitis is estimated to be about 0.98 cases per 100,000. Pneumococcal epiglottitis is responsible for 0.28 cases of epiglottitis per 100,000.

Croup or laryngotracheobronchitis is common in children aged 6 months to 6 years. Most cases of croup occur in children aged two years. Fortunately, despite the harsh breathing sounds, the condition is self-limiting.

Pertussis is responsible for a whooping cough, another URI that has significantly decreased after the introduction of pertussis vaccination. The current incidence of a whooping cough due to pertussis is estimated to be 9 per 100,000.

URIs are usually seasonal and most cases occur in fall or winter. It is hypothesized that cold weather increases indoor time and therefore puts us at prolonged exposure with those already infected.

Additionally, low humidity in winter is thought to be a significant factor in the thrive and increased the virulence of the different viruses implicated with URIs.

The common cold appears to be more common in young women. Epiglottitis, on the other hand, is more common in men. Croup, for obscure reasons, is more common in boys rather than girls.

Classification of URIs

Upper Respiratory tract infection (URTI)

Lower Respiratory tract infection (LRTI)

Infection from nose to epiglottis

Infection of the organ present from epiglottis to alveoli

Disease that comes under URTI are

Common cold

Pharyngitis

Epiglottitis

Rhinitis

Sinusitis

Influenza

Disease that comes under LRTI are

Laryngitis

Laryngotracheitis

Bronchitis

Bronchiolitis

Pneumonia

Some author called the term URTI as a misnomer as most of the patients with URTI has the symptoms of LRTI or most of the cases also has lower respiratory tract infection.

Etiologies of URIs

URIs can be caused by several viral and bacterial pathogens. The most commonly implicated viruses with URIs are rhinoviruses, coronaviruses, adenoviruses, and coxsackieviruses.

Image: “Epstein-Barr virus taken through an electron microscope.” by Linda Bartlett (Photographer) – This image was released by the National Cancer Institute, an agency part of the National Institutes of Health, with the ID 2105. License: Public Domain

The common cold is usually related to the rhinoviruses while coronaviruses can also account for a significant number of the cases. Adenoviruses can also cause nasopharyngitis.

Pharyngitis is usually caused by viruses by the recognition of group A streptococcus. Common viruses that are implicated with pharyngitis include adenovirus, the influenza viruses, and Epstein-Barr virus.

Group A streptococcal infection is responsible for up to 15% of the cases of pharyngitis in adults and 30% in children. Therefore, the early recognition of bacterial streptococcal pharyngitis is essential to prevent complications.

Patients with rhinosinusitis usually have another viral URI such as rhinovirus, coronavirus, or influenza A or B infection. These patients can have signs of sinusitis on computed tomography, which usually goes without any complications.

Secondary bacterial infection, however, can happen in few cases. Common organisms are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus.

Epiglottitis has been historically linked to Haemophilus influenzae but since the introduction of the Hib vaccine, the incidence of acute epiglottitis decreased dramatically. On the other hand, cases of streptococcus epiglottitis are becoming more commonly identified nowadays.

Croup can be caused by parainfluenza viruses types 1, 2 and 3. In few children, the cause is the influenza viruses.

Pathophysiology of URIs

Patients need to come in contact with an infected person or with inanimate objects that have been contaminated with the infecting organism. Once the person’s hand becomes contaminated with the potential pathogen, he or she can introduce the organism to him/herself when they touch the nose or the mouth. Viral or bacterial inoculation happens which is followed by the invasion of the mucosa lining the upper respiratory airway.

In addition to the virulence of the infecting organism, the person’s genetic susceptibility also plays a role in determining who is more likely to get sick once in contact with someone with URIs. Certain polymorphisms related to the immune system put the patient at an increased risk of developing severe influenza illness once exposed to the H1N1 or the H5N1 influenza viruses.

Details of Different URIs

Common Cold

The common cold is the commonest URTI mostly caused by viruses and is very contagious.

Causative organisms

Influenza viruses

Picornaviruses like (Coxsackie, Reo, Echo, and rhinovirus)

Respiratory Syncytial Virus

Parainfluenza virus

Adenovirus

Pathogenesis

The virus invades the nasal mucosa causing an immediate irritative reaction resulting in the secretion of large quantities of mucous and cells. Within 24 hours a secondary infection can intervene converting watery nasal discharge to purulent form.

Sign and Symptoms

Sneezing

Rhinorrhoea

Nasal congestion

Sore throat

Non-productive cough

Pain in the eyes

Headache

Malaise and Myalgia

Fever is uncommon but some patient can get fever

Conjunctivitis can occur in adenovirus infection

Some time it present with skin rash with enterovirus infection

On examination, post-nasal discharge, erythema around the nose and glossy nasal mucosa may be found, the pharynx shows congestion with some form of exudates. Exudates can also be present on tonsils. Jugulo-gastric lymph node may be enlarged and tender in some patients.

Complications

Sinusitis

Otitis media

Croup

Secondary bacterial pneumonia

Laboratory Investigation

Real-time polymerase chain reaction (RT-PCR) or isolation of the virus in culture or four-fold increase in virus-specific circulating antibodies are used for confirmation of the diagnosis. The clinical specimen used for this purpose are nasopharyngeal swab, nasal swab, pharyngeal swab and aspirate in case of intubated patients.

Treatment

Common cold usually treated empirically. The mainstay of treatment is symptomatic and supportive treatment. Bed rest adequate fluid, anticholinergic nasal spray, saline nasal drops, nasal decongestants like xylometazoline and oxymetazoline are used for symptomatic relief.

Pharyngitis

Definition and pathogenesis

Pharyngitis is defined as the inflammation of the pharynx, hypopharynx, uvula, and tonsils. It is usually of infectious etiology and the majority of causes are the viral origin. A beta-haemolytic streptococcus is common in children aged 4 to 7 years. persons with oro-genital contact, gonococcal pharyngitis can occur. Oral thrush involving pharynx can occur in the immunocompromised patient.

Identification of beta-haemolytic streptococci by this method is of paramount importance as it is associated with the development of rheumatic heart disease

Complications

Suppurative complication

Non-suppurative complication

Sinusitis

Otitis media

Epiglottitis

Mastoiditis

Peri-tonsillar abscess

Retropharyngeal abscess

Suppurative cervical lymphadenitis

Pneumonia

Airway obstruction

Thrombocytopenia

Myocarditis

Pericarditis

Encephalitis

Meningitis

Toxic shock syndrome

Acute rheumatic fever

Acute inflammatory demyelinating polyneuropathy

Treatment

The mainstay of treatment is symptomatic and supportive treatment. Some patient may require antibiotic for secondary bacterial infection or infection with beta hemolytic streptococci. Viral pharyngitis is self-limiting and resolves spontaneously. However, the clinician should be aware of a potential complication.

Epiglottitis

It is the infection of the epiglottis. Mostly it is a viral infection but sometime it may be of bacterial origin.

Epidemiology

It can occur at any age

Hemophilus influenza type B is mostly associated with Epiglottitis but current trend shows the rising trend of infection with beta haemolytic streptococci after mass vaccination against influenza virus

The incidence of acute epiglottitis in adults ranges from 0.97 to 3.1 per 100,000, with a mortality of approximately 7.1%

There is no seasonal variation in the incidence of epiglottitis

Sign and symptoms

Throat discomfort

Odynophagia

Cough

Difficulty in swallowing with sitting up and leaning forward position

Constitutional symptoms like body-ache, fever, myalgia, and malaise

Dysphagia, drooling, and stridor subsequent to thermal or caustic injury to epiglottis

Differential Diagnosis

Croup

Foreign body in airway

Bacterial tracheitis

Retropharyngeal abscess

Laboratory diagnosis

Antero-posterior radiographs of the neck are helpful in confirming the diagnosis and helps in ruling out the presence of the foreign body

“Thumb sign” in radiograph is indicative of sever acute epiglottitis

Laboratory tests are usually not helpful

Performing a flexible fiber optic laryngoscopy in a controlled clinical setting is reliable

Ultrasonography has been described as a way to investigate the epiglottis by visualization of the “alphabet P sign” in a longitudinal view through the thyrohyoid membrane

Complication

Death from asphyxia

Secondary bacterial infection

Pneumonia

Treatment

Viral epiglottitis is self-limiting and require only supportive treatment

Patients with secondary bacterial infection or with complication or epiglottitis of bacterial origin may require antibiotics. Broad-spectrum antibiotics like chloramphenicol or co-amoxiclav are the antibiotic of choice

Rhinitis

Definition

It is defined as the inflammation of the membranes lining the nose and it is characterized by nasal congestion, rhinorrhoea, sneezing, itching, conjunctival symptoms and other constitutional symptoms.

Classification

Rhinitis can be classified according to its etiology i.e. allergic or non-allergic

Allergic

Non-allergic

Seasonal (e.g. pollens)

Perennial (e.g. house dust, mites)

Occupational (e.g. animal antigens)

Infectious rhinitis

Acute (Viral/ bacterial)

Chronic (Specific bacterial & fungal or non-specific as in case of immunodeficiency disorder)

Infectious rhinitis without eosinophilia

Rhinitis with eosinophilia syndrome

Vasomotor rhinitis

Hormonal like in menstruation, pregnancy, hypothyroidism

Occupational

Food induced or gustatory rhinitis

Pathogenesis

Allergic rhinitis is due to inflammation in the nose which is immunoglobulin specifically IgE mediated. It is mostly due to acute exposure to inciting allergens. Non-allergic rhinitis pathogenesis varies according to their etiology but the main pathogenesis lies in the inflammation of nasal mucosa.

Signs and symptoms

Nasal congestion

Rhinorrhoea

Sneezing

Itching

Conjunctival symptoms

Other constitutional symptoms like fever, malaise etc.

Diagnosis

Identification of etiological cause is based on the pattern, chronicity and seasonal variation of symptoms, history of medication, the presence of co-existing conditions, occupational exposures, environmental history and identification of precipitating factors.

Influenza

Definition:

Influenza is an acute respiratory illness caused by infection with influenza viruses. This disease affects the upper or the lower respiratory tract and it’s usually associated with systemic manifestations such as fever, headache, myalgia, and weakness.

Etiology

Influenza viruses are members of the Orthomyxoviridae family, of which influenza A, B, and C viruses constitute three separate genera.The designation of influenza viruses as type A, B, or C is based on antigenic characteristics of the nucleoprotein (NP) and matrix (M) protein antigens.

Influenza A viruses are further subdivided (subtyped) on the basis of the surface hemagglutinin (H) and neuraminidase (N)antigens. Influenza A has 18 distinct H subtypes and 11 distinct N subtypes, of which only H1, H2, H3, N1, and N2 have been associated with epidemics of disease in humans.

Influenza B and C viruses are designated similarly to influenza A viruses, but H and N antigens from these viruses do not receive subtype designations.

Epidemiology

Influenza outbreaks occur virtually every year, although their extent and severity vary widely. Global pandemics have occurred at variable intervals, but much less frequently than interpandemic outbreaks. The most recent pandemicemerged in March of 2009 and were caused by an influenza A/H1N1 virus that rapidly spread worldwide over the next several months. The most extensive and severe outbreaks of influenza arecaused by influenza A viruses, in part because of the remarkable propensityof the H and N antigens of these viruses to undergo periodicantigenic variation.

Pathogenesis

The initial event in influenza is infection of the respiratory epithelium with influenza virus acquired from respiratory secretions of acutely infected individuals. In all likelihood, the virus is transmitted via aerosols generated by coughs and sneezes, although transmission through hand-to-hand contact, other personal contact, and even fomites may take place.Experimental evidence suggests that infection by a small particle aerosol (particle diameter <10 μm) is more efficient than larger droplets.

Initially, viral infection involves the ciliated columnar epithelial cells, but it may also involve other respiratory tract cells, including alveolar cells, mucous gland cells, and macrophages.In experimentally induced infection, the incubation period of illness has ranged from 18 to 72 h, depending on the size of the viral inoculum.

Signs and symptoms

Fever

Headache

Chills with rigor

Myalgia and malaise

Cough

Sore throat

However, the spectrum of clinical presentations is wide, rangingfrom a mild, afebrile respiratory illness similar to the common cold(with either a gradual or an abrupt onset) to severe prostration withrelatively few respiratory signs and symptoms.

Physical findings are usually minimal in uncomplicated influenza. Early in the illness, the patient appears flushed, and the skin is hot and dry, although diaphoresis and mottled extremities are sometimes evident, particularly in older patients. Examination of the pharynx may yield surprisingly unremarkable results despite a severe sore throat, but injection of the mucous membranes and postnasal discharge are apparent in some cases.In uncomplicated influenza, the acute illness generally resolves over 2—5 days, and most patients have largely recovered in 1 week, although a cough may persist 1—2 weeks longer.

Complications

Primary influenza viral pneumonia

Secondary bacterial pneumonia

Mixed viral and bacterial pneumonia

Myositis, rhabdomyolysis and myoglobinuria

Myocarditis and pericarditis

Encephalitis and transverse myelitis

Reye’s syndrome

Toxic shock syndrome

Laboratory diagnosis

Throat swab, noso-pharyngeal swab, or washes or sputum culture

RTPCR is most sensitive and specific

Rapid diagnostic test

Tissue culture

Serological test

Differential diagnosis

Mycoplasma pneumonia

Streptococcal pharyngitis

Early bacterial pneumonia

Treatment

Specific antiviral therapy is available for influenza: the neuraminidase inhibitors zanamivir

and oseltamivir for both influenza A and influenza B and the adamantane agents amantadine and rimantadine for influenza A. (1—6)

Clinical Presentation of URIs

The symptoms of Influenza, other URIs and allergies can overlap. Patients with the common cold usually develop it within 2 to 3 days after exposure and include rhinorrhea, nasal congestion, and sneezing. Patients can also complain from a sore throat and painful swallowing. A cough can be a symptom in some cases. Patients might develop a fever for a day or two.

Patients with bacterial pharyngitis might have a low-grade fever. Children can develop a skin rash. Unfortunately, history taking alone is usually not sufficient to exclude streptococcal pharyngitis.

The presence of anterior cervical lymphadenopathy is not characteristic of bacterial infection. The presence of tonsils exudates, tender anterior cervical lymph nodes and the absence of conjunctivitis, cough, and rhinorrhea are suggestive of bacterial rather than viral pharyngitis.

Patients with bacterial sinusitis can develop persistent nasal discharge for more than 10 days, worsening of their cough and fever, or develop a severe cough and fever from the start for three consecutive days.

Patients with epiglottitis usually complain of a sore throat, muffled sound, fever, drooling and can present the tripod position.

Diagnostic Workup in URIs

The identification of the exact infecting organism should be attempted only when specific treatment can be provided or in the immunocompromised patient. Rapid tests are available for the detection of influenza and parainfluenza viruses. Viral cultures are the standard criterion for the identification of the viral etiology of the URI but the results are usually available too late to alter the medical treatment, two to four weeks.

Complete blood count is helpful in excluding possible bacterial infections which are characterized by neutrophilia. Unfortunately, leukocytosis is rarely seen in URIs and complete blood count is usually not helpful in most cases.

Patients presenting with symptoms consistent with the common cold should not be offered routine imaging studies. Patients presenting with high fever, tender neck examination and signs suggestive of peritonsillar abscess need specific imaging studies including x-rays.

Patients with suspected group A streptococcal infection should undergo throat swab testing for group A streptococcus detection by rapid antigen testing, culture or both. Positive rapid antigen detection testing for group A streptococcus is highly specific and warrants specific treatment.

On the other hand, negative results should be backed up by a negative throat swab culture. Routine testing for streptococcal antibodies including the antistreptolysin O antibody is not helpful in the identification of acute infection because these antibodies usually peak 5 weeks after the infection.

Patients with suspected bacterial sinusitis should undergo computed tomography imagingof the sinuses. Computed tomography imaging should be preserved only for bacterial cases because it can be positive in up to 80% of the cases of uncomplicated rhinosinusitis.

Pertussis is usually a clinical diagnosis. Rapid direct fluorescent antibody testing can be used to confirm the diagnosis if needed. Patients with possible epiglottitis should undergo neck x-ray which is usually enough to exclude the diagnosis.

Treatment of URIs

Treatment of URIs is usuallysymptomatic but can be sometimes specific to the exact etiology or disease process.

Treatment of the common cold

Patients with symptoms consistent with uncomplicated common cold should drink plenty of water, might benefit from steamy baths and can use nasal decongestants for a limited period of time. Nonsteroidal anti-inflammatory drugs can be used to alleviate pain and inflammation. No specific antiviral treatment is usually indicated.

Treatment of influenza

Antiviral therapy can be helpful early in the disease as it was found to decrease the duration and the severity of the illness. Additionally, annual influenza vaccination not only decreases the risk of developing influenza during the season but also decreases the severity of the symptoms if one acquires the infection. Nonsteroidal anti-inflammatory drugs, drinking plenty of water and decongestants are also helpful.

Treatment of Rhinosinusitis

Symptomatic treatmentof viral rhinosinusitis is usually sufficient. Patients with suspected bacterial sinusitis should receive high-dose amoxicillin/clavulanate as first line therapy. Patients allergic to penicillins can receive doxycycline or levofloxacin. Patients who are not responsive to initial antibiotic treatment should undergo culture and sensitivity testing to confirm the infecting organism and its resistance profile.

Treatment of croup

Inhaled corticosteroids in addition to intravenous steroids are helpful in alleviating the symptoms of croup. Additionally, fluid replacement therapy should be started in children to avoid dehydration. Inhaled racemic epinephrine can also provide symptomatic relief.

Treatment of epiglottitis

Intravenous administration of antibiotics is indicated and should be started before the availability of the culture results. Ceftriaxone and cefuroxime are common first-line therapies for epiglottitis. Close contacts of the patient should also receive prophylactic antibiotic therapy.

Treatment of group A streptococcus pharyngitis

Group A streptococcus is sensitive to amoxicillin and penicillin. Therefore, oral administration of one of these two antibiotics is usually sufficient. Patients with non-anaphylactic shockto penicillins can receive a first generation cephalosporin. Patients with severe allergies should receive clindamycin, azithromycin or clarithromycin.

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